Patent GB-876192-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J75/00
Filed: 1960-03-14
Abstract: The invention comprises compounds having the formula: <FORM:0876192/IV (b)/1> wherein R is hydrogen, a lower alkyl radical containing from 1-8 carbon atoms inclusive, a o -carboxy-lower-hydrocarbyl radical including alkali metal salts thereof, or a disubstituted amino methylene radical wherein the disubstituted amino group is dilower alkylamino, wherein the alkyl group contains from 1-8 carbon atoms inclusive; or lower alkylbenzylamino wherein the alkyl group contains from 1-8 carbon atoms inclusive, a dibenzylamino, a pyrrolidino, a piperidino or morpholino radical including acid addition and quaternary ammonium salts thereof, Y is a b -hydroxymethylene group or carbonyl group, Z is hydrogen, fluorine, chlorine or bromine, o  is a methyl radical or fluorine and the 1,2-linkage represents a single or a double bond linkage and a process for the preparation thereof which comprises esterifying the corresponding 17a -hydroxy compound with an acid anhydride in the presence of an acidic esterification catalyst and then if desired thereafter hydrolysing any 3-enol ester formed under mild conditions with a base.  Compounds in which Z is fluorine are obtained from compounds in which Z is hydrogen by a dehydrating an 11b -OH compound to form a 9(11)-double bond, reacting the thus-obtained compound with hypohalous acid to form a 9-halo compound, reacting the 9-halo compound with a base to form a 9b ,11b -epoxy compound which with hydrogen fluoride gives the corresponding 9a -fluoro-11 b -hydroxy compound.  Illustrative products of the invention are 6a -methyl-9a -fluoro-11b ,17a -dihydroxy -4- pregnene-3,20-dione 17-acetate, 6a ,9a -difluoro-11 b ,17a -dihydroxy-4-pregnene-3,20-dione 17-acetate and the corresponding 1,4-pregnadienes.ALSO:Pharmaceutical compositions comprise compounds having the formula <FORM:0876192/VI/1> wherein R is hydrogen, a lower alkyl radical containing from 1-8 carbon atoms inclusive, a o -carboxy lower hydrocarbyl radical including alkali metal salts thereof, or a disubstituted amino methylene radical wherein the disubstituted amino group is dilower alkylamino, wherein the alkyl group contains from 1-8 carbon atoms inclusive, or lower alkylbenzylamino wherein the alkyl group contains from 1-8 carbon atoms inclusive, a dibenzylamino, a pyrrolidino or morpholino radical including acid addition and quaternary ammonium salts thereof, Y is a b -hydroxymethylene group or carbonyl group, Z is hydrogen fluorine, chlorine or bromine, W is a methyl radical or fluorine, and a pharmaceutical diluent.  They are administered orally, topically or parenterally, e.g. in solutions, suspensions, lotions, creams, ointments, salves, jellies, tablets, powders, pills or capsules, with or without antibiotics, e.g. penicillins, neomycin, tetracycline, bacitracin, novobiocin, erythromycin, polymyxin B sulphate, gramicidin, streptomycin sulphate, dihydrostreptomycin and chloramphenicol.  A dermatological and ophthalmic ointment comprises 6a  - methyl - 9a  - fluoro - 11b ,17a  - dihydroxy - 1,4 - pregnadiene - 3,20 - dione - 17 - acetate to which neomycin sulphate may be added.